PROJECT SUMMARY/ABSTRACT MRI relaxometry has been applied to improve early diagnosis and prognosis for a wide range of diseases. However, one typical obstacle of integrating quantitative MRI into clinical protocols is the long acquisition time. Furthermore, it is an essential but sometimes overlooked step to investigate quantification variability across sites and MR systems in order to validate MR imaging biomarkers and to apply the measures in large scale multi- vendor multi-site trials. Specifically, there is a lack of systematic evaluation of inter-vendor inter-site variability of T1? imaging, even though it has been widely applied in neural-, liver-, cardiac-, oncology-, and musculoskeletal- (MSK) imaging. Neither commercial T1? phantoms are available. The proposed study is addressing these significant gaps and aims to develop and cross-validate novel fast MR T1? and T2 imaging methods on MR systems from multiple vendors, followed by feasibility evaluation in patients at risk for osteoarthritis. Osteoarthritis (OA) affects over 27 million people in the US. No disease modifying OA drugs (DMOADs) are available, despite extensive effort. One hurdle for developing DMOADs is the lack of sensitive and reliable non-invasive biomarkers that can detect treatment effects over a short time window. Such biomarkers would also benefit clinical practice by identifying patients at risk for developing OA or at an early disease stage, when behavior modification strategies are shown to be most effective in slowing down the disease progression. There is a pressing, unmet clinical need for robust assessment of early degeneration, which is critical to support a paradigm shift of OA management from palliation of late disease towards prevention through early diagnosis and early treatment/interventions. Cartilage MR T1? and T2 measures have been shown to be promising imaging biomarkers for early cartilage degeneration. However, many challenges remain to clinically applying these techniques, including lack of standardized acquisition and analysis methods, long acquisition time, and uncertainty of variations between different MR systems. In this study, we will develop novel accelerated T1? and T2 imaging methods, implement these techniques on MR systems of three major vendors (Siemens, GE and Philips), systematically evaluate inter-vendor inter-site variation of these measures using dedicated T1? and T2 calibration phantoms (to be developed in this study) and traveling subjects, investigate the source(s) and magnitude of the differences, explore methods to mitigate the variability, and demonstrate the feasibility of the newly developed acceleration techniques to quantify cartilage degeneration longitudinally in a multi-vendor setting. Successful implementation of the proposed study will provide a full package of T1? and T2 imaging that will be ready for dissemination and will help to pave the way towards large-scale multi-vendor, multi-site trials using T1? and T2 imaging, facilitate clinical translation of these quantitative MR techniques, and ultimately transform patient management of OA and other disorders using quantitative imaging biomarkers.